Funny you mention Devin Naar because he is one of the scholars I have consulted on this question. According to Dr. Naar (who also said his expertise lies mostly in the 19th and 20th Centuries) it seems unusual for there to have been an Iberian origin Jew in Salonica before 1492, but he supposes it to be possible.
I believe the source of the factoid about Spain may be Friedman's Utser HaRabanim (#16786) in which is specifically stated that R' Akiva the Alter is an exile from Spain, and I do remember reading somewhere that the problems in Spain began well before 1492, so it might stand to reason that there were refugees already there in the mid-14th Century.
For me, what seems to be a key fact is that we do have evidence of an Ashkenazic Synagogue going up in Salonika in 1376 just around the time when the Jews were expelled from Hungary (1376). Then we see that R' Akiva's grandson thrives in Buda before fleeing to Prague. There doesn't appear to be any descending lines that remain in Ottoman lands after the 1540s.
I ask myself, if the family had been originally Sephardic, then why wouldn't any descending lines have chosen to remain in Ottoman lands after Salonika was overtaken by Ottomans in 1541? After all, many Sephardim found themselves welcome in Ottoman lands and stayed there for centuries. Interestingly, there is a citation in the article: History of Jews in Thessalonika on Wikipedia, which states: "Salonika's registers indicate the presence of "Buda Jews" after the conquest of that city by the Turks in 1541." Could it be that Ashkenazim did not feel the same desire to remain in Ottoman territory and thus opted to try their luck back in Hungary, Czechia, and Germany? Another question I ask myself is whether, for political reasons, the family wanted to give the appearance of being Sephardim in the hopes of receiving more favorable treatment in Central Europe (cf. Zamosc, etc,).
So it does seem to be a little more reasonable at this point that the family began as Ashkenazim fleeing Hungary to a Hellenic Salonika and then eventually returned to their place(s) of origin as conditions allowed (perhaps even under the guise of being Sephardim).
It is difficult to explain otherwise how the R' Akiva HaCohen the Elder's descending lineage would take such a central role in the development of Ashkenazic theological history: among other things: it is a granddaughter who marries a son of the first Horowitz (see below about Horowits family), a 3x ggs who becomes a Dayan in Frankfurt, another 3x ggs who marries a daughter of the Maharal of Prague, and a 5x ggs (the SHaCH) who marries a 2x granddaughter of the Rema, among others! Looked at in this light, the family of R' Akiva the Elder was and remained Ashkenazic from the beginning, or represents an astonishing introgression of a Sephardic lineage into the mainstream of several Ashkenazic rabbinical families.
I am not studying the Horovits family tree, but I remember reading a discussion about whether that family may have been Sephardic originally, eventually leading GENI curators to sever a proposed connection between Rabbi Joseph HaLevi and the Benveniste tree, because that connection was deemed to be a fabrication of the 19th Century. I wonder whether the claim that R' Akiva was Sephardic is another example of erroneous information (which may have been fabricated for political purposes in earlier times).
My apologies for such a long post, but this is a complex and deep topic, which is why I am seeking consultation with as many Jewish historians as I can find.
The reason this is important to me (and many others I imagine) is that this fork in the road determines whether to look for prior genealogy in Spain or Hungary. The take-home message is this: R' Akiva the Elder may not have been born in Spain and instead may have been one of the Buda Jews who expelled from Hungary in 1376 and lived in Salonika for several generations before returning to Hungary and other predominantly Ashkenazic lands. I am merely suggesting that this is a plausible possibility, subject to the opnions of more learned analysts.